A stable pattern of EEG spectral coherence distinguishes children with autism from neuro-typical controls - a large case control study.
- Authors
- Duffy, Frank H; Als, Heidelise
- Year
- 2012
- Journal
- BMC medicine
- PMID
- 22730909
- DOI
- 10.1186/1741-7015-10-64
- PMCID
- PMC3391175
BACKGROUND: The autism rate has recently increased to 1 in 100 children. Genetic studies demonstrate poorly understood complexity. Environmental factors apparently also play a role. Magnetic resonance imaging (MRI) studies demonstrate increased brain sizes and altered connectivity. Electroencephalogram (EEG) coherence studies confirm connectivity changes. However, genetic-, MRI- and/or EEG-based diagnostic tests are not yet available. The varied study results likely reflect methodological and population differences, small samples and, for EEG, lack of attention to group-specific artifact. METHODS: Of the 1,304 subjects who participated in this study, with ages ranging from 1 to 18 years old and assessed with comparable EEG studies, 463 children were diagnosed with autism spectrum disorder (ASD); 571 children were neuro-typical controls (C). After artifact management, principal components analysis (PCA) identified EEG spectral coherence factors with corresponding loading patterns. The 2- to 12-year-old subsample consisted of 430 ASD- and 554 C-group subjects (n = 984). Discriminant function analysis (DFA) determined the spectral coherence factors' discrimination success for the two groups. Loading patterns on the DFA-selected coherence factors described ASD-specific coherence differences when compared to controls. RESULTS: Total sample PCA of coherence data identified 40 factors which explained 50.8% of the total population variance. For the 2- to 12-year-olds, the 40 factors showed highly significant group differences (P < 0.0001). Ten randomly generated split half replications demonstrated high-average classification success (C, 88.5%; ASD, 86.0%). Still higher success was obtained in the more restricted age sub-samples using the jackknifing technique: 2- to 4-year-olds (C, 90.6%; ASD, 98.1%); 4- to 6-year-olds (C, 90.9%; ASD 99.1%); and 6- to 12-year-olds (C, 98.7%; ASD, 93.9%). Coherence loadings demonstrated reduced short-distance and reduced, as well as increased, long-distance coherences for the ASD-groups, when compared to the controls. Average spectral loading per factor was wide (10.1 Hz). CONCLUSIONS: Classification success suggests a stable coherence loading pattern that differentiates ASD- from C-group subjects. This might constitute an EEG coherence-based phenotype of childhood autism. The predominantly reduced short-distance coherences may indicate poor local network function. The increased long-distance coherences may represent compensatory processes or reduced neural pruning. The wide average spectral range of factor loadings may suggest over-damped neural networks.
Standard EEG electrode names and positions. Head in vertex view, nose above, left ear to left. EEG electrodes, Z, Midline, FZ, Midline Frontal; CZ, Midline Central; PZ, Midline Parietal; OZ, Midline Occipital. Even numbers, right hemisphere locations; odd numbers, left hemisphere locations, Fp, Frontopolar; F, Frontal; C, Central; T, Temporal; P, Parietal; O, Occipital. The standard 19, 10 to 20 electrodes are shown as black circles. An additional subset of five, 10-10 electrodes are shown as open circles.
Graphic representation of 33 coherence factor loadings. EEG coherence factor loadings. Heads in top view, scalp left to image left, nose above; Factor number is above heads to left and peak frequency for factor in Hz is above to right. Lines indicate top 15% coherence loadings per factor: Red = increased coherence in ASD-group; Yellow = decreased coherence in ASD-group. Involved electrodes shown as small white circles. Uninvolved electrodes are not shown.
| # | Section | Preview |
|---|---|---|
| 20 | Methods β Measurements and data analysis β EEG data acquisition | Registered EEG technologists, naΓ―ve to the study's goals, and specifically trained and skilled inβ¦ |
| 21 | Methods β Measurements and data analysis β EEG data acquisition | Hz bandpass filtering and digitized at 256 Hz for subsequent analyses. All amplifiers wereβ¦ |
| 22 | Methods β Measurements and data analysis β Measurement issues and solutions | EEG studies are confronted with two major methodological problems. First is the management of theβ¦ |
| 23 | Methods β Measurements and data analysis β Measurement issues and solutions β Artifact management - Part 1: Unprocessed EEG signals | At the conclusion of each subject's data collection, digitized EEG data were inspected by the EEGβ¦ |
| 24 | Methods β Measurements and data analysis β Measurement issues and solutions β Artifact management - Part 1: Unprocessed EEG signals | Freihamer Strasse 18, 82116 GrΓ€felfing - Germany) software package. These combined techniquesβ¦ |
| 25 | Methods β Measurements and data analysis β Measurement issues and solutions β Calculation of spectral coherence variables | Approximately 8 to 20 minutes of awake state EEG data per subject were transformed by use of BESAβ¦ |
| 26 | Methods β Measurements and data analysis β Measurement issues and solutions β Calculation of spectral coherence variables | Spectral coherence was calculated, using a Nicoletβ’ (Nicolet Biomedical Inc., 5225 Verona Road,β¦ |
| 27 | Methods β Measurements and data analysis β Measurement issues and solutions β Calculation of spectral coherence variables | Furthermore, the quest for better measures of connectivity between brain regions in EEG and MRI hasβ¦ |
| 28 | Methods β Measurements and data analysis β Measurement issues and solutions β Calculation of spectral coherence variables | Spectral coherence measures were derived from the 1 to 32 Hz range, in 16, two-Hz-wide, spectralβ¦ |
| 29 | Methods β Measurements and data analysis β Measurement issues and solutions β Artifact management - Part 2: Coherence data | As has been recently discussed in a study of normal adults and adults with chronic fatigue syndromeβ¦ |
| 30 | Methods β Measurements and data analysis β Measurement issues and solutions β Artifact management - Part 2: Coherence data | and 1.0 Hz spectral components from these channels after EEG spectral analysis by Fast Fourierβ¦ |
| 31 | Methods β Measurements and data analysis β Measurement issues and solutions β Artifact management - Part 2: Coherence data | linear regression model where the dependent variables were those targeted for artifact reduction andβ¦ |
| 32 | Methods β Measurements and data analysis β Prevention of capitalization upon chance: Variable number reduction by creation of coherence factors | In order to facilitate subsequent statistical analysis, specifically in order to avoidβ¦ |
| 33 | Methods β Measurements and data analysis β Prevention of capitalization upon chance: Variable number reduction by creation of coherence factors | [56]. Varimax rotation enhances factor contrast yielding higher loadings for fewer factors whileβ¦ |
| 34 | Methods β Measurements and data analysis β Data analysis β Discrimination of subject groups by use of EEG spectral coherence variables | Two-group discriminant function analysis (DFA) [58-60] was used extensively in this study. Itβ¦ |
| 35 | Methods β Measurements and data analysis β Data analysis β Discrimination of subject groups by use of EEG spectral coherence variables | formed on all subjects but one. The left-out subject was subsequently classified. This initial leftβ¦ |
| 36 | Methods β Measurements and data analysis β Data analysis β Discrimination of subject groups by use of EEG spectral coherence variables | test-set (remaining 50% of the subjects - used to estimate prospective classification success). Theβ¦ |
| 37 | Methods β Measurements and data analysis β Data analysis β Factor description; relationship of PCA outcome factors to input coherence variables | Individual outcome factors were each formed as linear combinations of all input variables with theβ¦ |
| 38 | Methods β Measurements and data analysis β Age grouping | Given the wide age range (14 months to 18 years) of the subjects within the ASD- and C-groups andβ¦ |
| 39 | Methods β Measurements and data analysis β Age grouping | effect of age was removed from the 40 coherence variables generated on the 2- to 12-year-old totalβ¦ |
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